Chunk #13 — Results — Methadone dose genome-wide association study (GWAS) in the Yale-Penn OD sample identifies a significant association upstream of OPRM1 at rs73568641
Figure 2 displays the usual daily methadone dose for each AA subject, stratified by rs73568641 genotype. The association between methadone dose and rs73568641 was specific to AAs (EA n = 1,027, MAF = 0.17, P = 0.32, Supplemental Table 3), and no SNPs were genome-wide significant in the GWAS conducted in the EA sample (EA QQ plot is shown in Supplemental Figure 4). Manhattan plots are shown in Supplemental Figure 5. In an exploratory analysis across samples evaluating previously studied candidate alleles from genes encoding methadone metabolizing enzymes,44 we found suggestive evidence that the CYP2D6 loss of function variant rs3892097 is associated with lower methadone dose (AA and EA n = 1,410, P = 2.6 × 10−3) (Supplemental Table 4). A genome-wide meta-analysis of the AA and EA samples did not reveal additional genome-wide significant variants.
